22-32931181-G-T

Variant names:

• chr22-32931181-G-T
• rs183588
• NM_003490.4:c.461+209C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.461+209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 476,852 control chromosomes in the GnomAD database, including 230,163 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (72047 hom., cov: 32)
  • Exomes 𝑓: 0.99 (158116 hom.)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.461+209C>A		intron_variant	Intron 4 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.461+209C>A		intron_variant	Intron 4 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000472027.1	n.409C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147920 AN: 152152 Hom.: 71990 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.977

GnomAD4 exome AF: 0.987 AC: 320345 AN: 324582 Hom.: 158116 Cov.: 3 AF XY: 0.986 AC XY: 166899 AN XY: 169228

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.990

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.966

Gnomad4 FIN exome AF: 0.994

Gnomad4 NFE exome AF: 0.991

Gnomad4 OTH exome AF: 0.985

GnomAD4 genome AF: 0.972 AC: 148036 AN: 152270 Hom.: 72047 Cov.: 32 AF XY: 0.973 AC XY: 72384 AN XY: 74426

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.975

Alfa AF: 0.984 Hom.: 25012

Bravo AF: 0.971

Asia WGS AF: 0.974 AC: 3386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.014
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs183588; hg19: chr22-33327166;